Law enforcement officers have a higher prevalence of cardiovascular disease (CVD) than the general population which cannot be explained by an excess of conventional risk factors. CVD is an inflammatory disease and several aspects of the law enforcement profession, e.g. job-related stress, can affect inflammatory mediators. The objective of this proposal is to test the hypothesis that officers have a higher risk of cardiovascular disease due to alterations in pro- and anti-atherogenic inflammatory mediators which are associated with job-related stress. This hypothesis will be tested by pursuing two specific aims: 1) Quantify the levels of pro- and anti-atherogenic cytokines and other inflammatory mediators in law enforcement officers and 2) Determine the forms of job-related stress most associated with changes in these inflammatory mediators. Under the first aim, levels of pro-atherogenic C-reactive protein, fibrinogen, TNF- alpha, IL-1beta, IL-6, and IL-18 and anti-atherogenic IL-4 and IL-10 will be compared in law enforcement officers to an otherwise similar general population cohort. Under the second aim the association between these inflammatory mediators, a general measure of perceived stress, the job-related stress measures of vital exhaustion, job strain and effort-reward imbalance, and the stress biomarker of salivary cortisol will be determined. The rationale for the proposed research is that, once the pathogenesis of the increased arevalence of cardiovascular disease in this profession is understood, specific interventions can be designed to combat the identified risk factor(s). The proposed work is innovative because we have conceptually linked inflammatory mediators associated with cardiovascular disease and work-related factors that can affect these mediators to a demonstrated increased prevalence of cardiovascular disease in law enforcement officers. The proposed work is significant because it is expected to increase our understanding of the mechanisms underlying the pathogenesis of cardiovascular disease in this high stress occupation. [unreadable] [unreadable] [unreadable]